1. Field of the Invention.
The present invention relates generally to electrodes. In particular, the present invention relates to a pH buffered electrode for use in medical iontophoresis.
2. Description of the Prior Art.
The technique of iontophoresis employs an electric field to mobilize ionic medicaments through the skin. This therapeutic modality allows for the introduction of substances into the tissues and blood stream of a patient without the necessity of hypodermic injection and its concomitant untoward effects, such as pain and risk of infection. Delivery of drugs via iontophoresis also presents the advantage of avoiding first-pass metabolism of a medicament. When a medicament is taken orally and absorbed from the digestive tract into the blood stream, the blood containing the medicament first percolates through the liver, a metabolically active organ, before entering the general circulation for delivery to the target tissue. Thus much of the orally ingested medicament may be metabolically inactivated before it has a chance to exert its pharmacologic effect. Local delivery of medicaments, therefore, presents advantages over hypodermic injection, an invasive, inconvenient, and sometimes risky technique, and oral administration, a modality characterized by inefficiency and unpredictability.
The usefulness of electrodes in medical procedures is limited, however, by a finite incidence of skin burns resulting from the passage of current through the skin. The primary causative factor of this skin burning is an electrochemical mechanism whereby the applied current causes electrolysis of water and generates either H.sup.+ or OH.sup.- ions, which cause pH changes that ultimately lead to a burning of the skin under the electrode. For example, in an iontophoresis procedure to mobilize a positively charged medicament through the skin, an aqueous reservoir containing the positively charged medicament will be placed at the anode, or positive electrode. A negatively charged electrode or cathode, will act as an indifferent electrode. When current is applied to the iontophoresis system, the medicament will be driven toward and through the skin, but the application of the current at the positive electrode will also cause the following reaction: EQU 2H.sub.2 O.fwdarw.O.sub.2 +4H.sup.+ 4e.sup.-
The H.sup.+ ions will move rapidly to the skin, decrease the pH of the aqueous environment to dangerous levels, and ultimately cause a burning of the skin. At the cathode, in this example the indifferent electrode, the following reaction occurs: EQU 2H.sub.2 O+2e.sup.- .fwdarw.H.sub.2 +20H.sup.-
The OH.sup.- ions move rapidly to the skin, increase the pH of the aqueous environment at the electrode to dangerous levels, and ultimately cause a burning of the skin under the negative electrode. In an iontophoresis procedure to mobilize a negatively charged medicament through the skin, the same reactions will occur at the anode and cathode, with the cathode impregnated with medicament ions and the anode acting as the indifferent electrode. In a typical application of current through electrodes contacting the skin, the pH under the anode decreases to less than 1.5 (acidic), and the pH under the cathode increases to exceed 10 (basic). Application of current in an iontophoresis procedure, then, not only mobilizes the ionic medicament across the skin, but also causes the electrolysis of water and the generation of reactive H.sup.+ and OH.sup.- ions that cause a burning of the skin. In addition, a substantial amount of current is wasted in driving the H.sup.+ and OH.sup.- ions and the presence of these ionic species in the iontophoretic system aggravates the problem of quantification of the amount of medicament delivered during the iontophoretic procedure.
A substantial effort has been directed toward alleviating the problem associated with electrochemical burns in iontophoresis. One approach has been to introduce a buffer into the iontophoretic system. A buffer renders a solution more resistant to a change in pH following addition of acid (H.sup.+) or base (OH.sup.-) than does an equal volume of water. In this approach, a soluble buffer salt is included in the solution containing medicament ions. The buffer will be a weak acid or base that has been titrated with a strong base or strong acid to form a salt of the weak acid or weak base capable of scavenging H.sup.+ or OH.sup.- ions. In scavenging the undesirable H.sup.+ or OH.sup.- ions, the buffer will reduce the incidence of skin burns under the iontophoresis electrode.
This use of a buffer in an iontophoresis system, however, presents several problems. Firstly, buffer ion molecules and their complementary ions tend to be smaller and thus more mobile than medicament ions. When current is applied to an iontophoretic system containing a buffer, the buffer ions will move more rapidly toward and through the skin than the medicament ions. Thus, current is consumed in driving buffer ions across the skin instead of desirable medicament ions, and it is more difficult to quantify the amount of medicament driven through the skin. Although a buffer incorporated into an iontophoresis system could successfully scavenge undesirable H.sup.+ and OH.sup.- ions and reduce burning of the skin, the problems associated with mobile buffer ions overcome any advantage this approach might have. (Problems of this type are described in the Background section of U.S. Pat. No. 4,752,285.) Other methods and approaches to the electrochemical burn problem include maintaining the voltage at the interface of the electrode and the medicament solution below the electrolysis voltage of water (e.g. U.S. Pat. No. 4,752,285) or the use of a sacrificial electrode to minimize the production of unwanted species (e.g. U.S. Pat. No. 4,744,787). A continuing effort is under way to effectively alleviate the electrochemical burn problem associated with medical iontophoresis.